tbuckley/cabot-search huggingface dataset:
P1712: CORONAVIRUS ANXIETY LEVEL AND COVID 19 VACCINE ATTITUDE AMONG HEMATOLOGICAL MALIGNANCY PATIENTS
Authors: Z. Güven, M. Keklik, A. Ünal
Journal: HemaSphere (2022)

Background: The COVID-19 vaccine is the most essential tool for altering the pandemic’s trajectory. The pandemic’s control is complicated by society’s unwillingness to vaccination. Aims: The aim of this cross-sectional study was to assess patients with hematological malignancies’ attitudes regarding the COVID-19 immunization and to investigate COVID-19 anxiety in this susceptible population Methods: In this study, 165 patients with hematological malignancies were included. The COVID-19 anxiety situation was evaluated with the Coronavirus Anxiety Scale (CAS). COVID- 19 vaccine attitude was evaluated with the Vaccine Attitudes Review (VAX) Scale. Results: The mean CAS score was 2.42 (0 - 17). There were 22 (13%) participants with a mean CAS score of ≥9. Half of the participants had a CAS score of 0. The CAS score was higher in females (p= 0.023). Similarly, it was significantly higher in patients who were not in remission for hematological malignancy and who received active chemotherapy (p= 0.010). The mean VAX score was 49.07 ± 8.76 (27-72). Most of the participants (64%) had a neutral attitude towards COVID-19 vaccination. In a survey of 165 patients, 55% said that they were skeptical about vaccination safety, and 58% said that they were concerned about unintended side effects. In addition, 90% expressed moderate concerns about commercial profiteering. Natural immunity was preferred by 30% of the participants. There was no statistically significant correlation between CAS scores and Vaccine Attitudes Review (VAX) Scale. Summary/Conclusion: This study draws attention to the level of anxiety in patients with hematological malignancies of the COVID-19 pandemic. Negative attitudes towards the COVID-19 vaccine are worrisome for at-risk patient groups. We think that patients with hematological malignancies should be informed to eliminate their hesitations about COVID-19 vaccines.
P895: DARATUMUMAB, BORTEZOMIB, AND DEXAMETHASONE (D-VD) VERSUS BORTEZOMIB AND DEXAMETHASONE (VD) ALONE IN CHINESE PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED ANALYSIS OF LEPUS
Authors: W. Fu, W. Li, J. Hu, G. An, Y. Wang, C. Fu, L. Chen, J. Jin, X. Cen, Z. Ge, Z. Cai, T. Niu, M. Qi, X. Gai, Q. Li, W. Liu, W. Liu, X. Yang, X. Chen, J. Lu
Journal: HemaSphere (2022)

Background: D-Vd prolonged progression-free survival (PFS) and induced deeper and more durable responses versus Vd alone in patients with RRMM in the global phase 3 CASTOR study (Weisel K, et al. ASH 2019. Abstract 3192). Results from a prespecified interim analysis of the phase 3 LEPUS study (median follow-up, 8.2 months) showed significant clinical benefit with D-Vd versus Vd in Chinese patients with RRMM and a safety profile that was generally consistent with that of CASTOR (Lu J, et al. Clin Lymphoma Myeloma Leuk 2021. 21[9]:e699-e709). Aims: To examine updated efficacy of D-Vd versus Vd in LEPUS at a median follow-up of 25.1 months. Methods: In the randomized, multicenter, phase 3 LEPUS study (NCT03234972), Chinese patients with RRMM and ≥1 prior line of therapy were randomized 2:1 to 8 cycles (21 days/cycle) of Vd (bortezomib 1.3 mg/m2 SC on Days 1, 4, 8, and 11; dexamethasone 20 mg PO/IV on Days 1, 2, 4, 5, 8, 9, 11, and 12) ± daratumumab (16 mg/kg IV once weekly in Cycles 1-3, every 3 weeks in Cycles 4-8, and every 4 weeks thereafter until disease progression). PFS was the primary endpoint. Results: A total of 211 patients were randomized (D-Vd, n = 141; Vd, n = 70), with a median age of 61 (range, 28-82) years. Patients received a median of 2 (range, 1-11) prior lines of therapy; 79.1% of patients previously received bortezomib, 26.5% were refractory to lenalidomide, and 64.0% were refractory to their last prior line of therapy. At a median follow-up of 25.1 months, D-Vd prolonged PFS versus Vd alone (median: 14.8 vs 6.3 months; hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.24-0.51; P <0.00001). The PFS benefit of D-Vd versus Vd was maintained across subgroups, including patients with prior bortezomib (HR, 0.36; 95% CI, 0.25-0.53), patients with high-risk cytogenetics (HR, 0.41; 95% CI, 0.23-0.71), and patients who were refractory to last prior line of therapy (HR, 0.42; 95% CI, 0.27-0.65). Overall response rate (ORR; 84.7% vs 66.7%; P = 0.00314) and rates of very good partial response or better (71.5% vs 34.9%; P <0.00001) and complete response or better (40.1% vs 14.3%; P = 0.00016) were higher with D-Vd versus Vd. Median time to first response was numerically shorter (0.79 months vs 1.23 months) and median duration of response was numerically longer (16.8 months vs 9.0 months) with D-Vd versus Vd. The estimated 18-month overall survival rate was 78.8% in the D-Vd group and 65.8% in the Vd group. Summary/Conclusion: In this updated analysis of LEPUS, D-Vd continued to demonstrate substantial efficacy benefits versus Vd in terms of PFS, ORR, and depth of response. These data further support the use of D-Vd as a standard of care in Chinese patients with RRMM.
PB2106: REDUCTION OF METHOTREXATE (MTX) LEVELS AFTER GLUCARPIDASE IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) AT RISK OF CENTRAL NERVOUS SYSTEM (CNS) INVOLVEMENT WHO RECEIVE HDMTX: PHASE 2
Authors: A. De La Fuente, F. J. Peñalver, P. Herrera, R. Cordoba, C. Martinez Chamorro, M. T. Olave, I. Jarque, M. B. Navarro, M. Estévez
Journal: HemaSphere (2022)

Background: CNS relapse in patients with Diffuse Large B Cell Lymphoma (DLBCL) is usually an early complication and with poor prognosis. R-CHOP, the standard treatment for DLBCL plays a minimal role preventing leptomeningeal and/or brain parenchyma relapse. Risk factors have been previously identified for this complication and high dose intravenous methotrexate (HDMTX) has been suggested as an effective strategy to prevent CNS lymphoma relapse (GELTAMO guidelines Haematologica 2017 and British guidelines BJAEM 2020). Unfortunately the administration of HDMTX is related with risk of renal, hepatic and haematological adverse events. Aims: Primary objective is: To describe the reduction of MTX levels after systematic administration of reduced Glucarpidase doses (2,000 units) 12 hours following start of HDMTX infusion in DLBCL patients at high risk for CNS involvement, receiving multiple cycles of HDMTX. Secondary objectives are: To analyze the prophylactic effect of Glucarpidase administered after 12 hour of high-dose MTX (HDMTX) on the incidence and severity and duration of MTX related-toxicity (renal toxicity, mucositis, liver toxicity, neutropaenia, thrombocytopaenia). To assess the incidence of CNS relapse during one year To assess the length of hospital stay (LOS) during HDMTX therapy To analyze the appearance of antibodies against Glucarpidase To analyze the appearance of neutralizing antibodies against Glucarpidase The study is currently enrolling. ClinicalTrials.gov Identifier: NCT05022797 Methods: This is an open-label, interventional, non-randomized, phase 2, pilot, multicenter study in Diffuse large B-cell lymphoma (DLBCL) patients at high risk of CNS relapse to assess of prophylactic effect of 2,000 unit of Glucarpidase in MTX related-toxicity administered after 12 hours of HDMTX. This study will be performed in the context of in-patients setting for receiving the three HDMTX courses. Criteria for CNS involvement are concordant with those of the last approved version of the GELTAMO guideline for the diagnostic, prevention, and therapeutical management of Central Nervous System involvement in patients with diffuse large cell B Lymphoma (revised 2017) [1]. Inclusion criteria: Age 18 year and above, diagnosis with diffuse large B-cell lymphoma at high risk of CNS involvement and adequate haematological, renal and hepatic function. Criteria to consider risk of CNS involvement were: >=2 extranodal site involved plus an elevated LDH and/or lymphoma involvement of the testis, breast, adrenal gland or kidney In order to include patients without CNS involvement, patients will be included in the study with a negative result of the CSF cytometry flow test, which will be performed according to normal clinical practice. Results: Trial ongoing Image:Summary/Conclusion: Trial ongoing
PB1950: MASS CYTOMETRY ANALYSIS IDENTIFIES T CELL IMMUNE SIGNATURE FOR APLASTIC ANEMIA AND PREDICTS RESPONSE TO CYCLOSPORINE
Authors: L. Zhang, J. Mao, Y. Lian, Q. Liang, H. Pan, Z. Gao, W. Li, J. Zhao, L. Fang, Y. Chu, W. Yuan, J. Shi
Journal: HemaSphere (2022)

Background: Aplastic anemia (AA) is a bone marrow failure syndrome attacked by autologous T cells. Cyclosporine is often taken for non-severe AA which is accounting for 80% of AA. Although effective, the response rate to cyclosporine is only around 50%. Emerging data support that T cell subpopulations, expression of transcription factors and immune checkpoint molecules are critical to regulate pathophysiology of AA. It’s also verified that T cell egress and activation play an important role in autoimmune diseases. Aims: We hypothesis that defining T cell immune signature will facilitate the development of predicting cyclosporine response and exploring novel immune-based therapeutics. Methods: Here, we performed mass cytometry for phenotypic and functional immune analysis on clinical samples from AA patients receiving cyclosporine treatment and demonstrated a significant heterogeneity on expression of inhibitory molecules, T cell trafficking and cytokines. Results: T-cell expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) was upregulated following response to cyclosporine and a lower level of CTLA-4 on CD8+ T cells was correlated to better treatment response. Moreover, higher expression of sphingosine-1-phospharylation receptor 1 (S1P1) on naïve T cells and higher level of interleukin-9 (IL-9) on T helpers predicted a worse response to cyclosporine. Therefore, this immune signature has a strong predictive value for clinical response. Summary/Conclusion: Collectively, our study suggests that immune-based analysis may predict clinical response to cyclosporine and provide a therapeutic strategy to improve the treatment of AA.
P1648: ANALYSIS OF ANKRD26 GENE 5’UTR VARIANTS IN A COHORT OF CZECH PATIENTS WITH SUSPECTED HEREDITARY HEMATOLOGICAL DISORDER
Authors: K. Stano Kozubik, J. Trizuljak, Z. Vrzalova, L. Radova, I. Blahakova, J. Stika, P. Smejkal, V. Bergerova, J. Hynst, S. Pospisilova, M. Doubek
Journal: HemaSphere (2022)

Background: Variants in the 5‘UTR region c.-116C - c.-140C of ANKRD26 gene were described as causal for ANKRD26-related thrombocytopenia (THC2). This autosomal dominant disorder presents as mild to moderate thrombocytopenia with minimal symptoms but for the carrier means increased risk of malignancy, mainly myeloproliferation. Recently, the c.-140C>G variant was described in dbSNP in 6.2% non-Finnish European population. Aims: This fact raises the question whether the ANKDR26 c.-140C>G variant is a pathogenic mutation responsible for the THC2 phenotype or, given its frequency, a population polymorphism. Methods: Exome sequencing (WES) was performed on a cohort of patients with suspected inherited hematological disorder. WES results were confirmed by Sanger sequencing. Subsequently, the cohort of patients with a variant in 5’UTR in ANKRD26 gene was analyzed with respect to clinical symptoms. Finally, variants in the 5’UTR of ANKRD26 gene were searched in the genomes of the healthy Czech population. Results: WES analysis was performed on the cohort of 53 patients from 31 families with following results: 12 individuals from 5 families carry heterozygous, 1 homozygous c.-140C>G variant, and 3 individuals from 1 family heterozygous c.-118C>T variant of ANKRD26 gene. No other gene variant was detected that was causal for their phenotype except for that found in the 5’UTR of ANKRD26 gene. The c.-118C>T variant was already published by several authors and was always associated with thrombocytopenia. From clinical data: Thrombocytopenia was present in 4 individuals: 1 with c.-140C>G variant and 3 with c.-118C>T variant. Moreover, 3 individuals with c.-140C>G variant were diagnosed with the oncologic disorder: 2 with essential thrombocythemia and 1 with multiple myeloma. Aggregation test results were available from 9 individuals from 4 families with c.-140C>G variant: 5 individuals showed platelet hypoaggregation after Collagen, ADP, and Epinephrine – Table 1. Besides, one individual showed hypoaggregation similar to von Willebrand disease IIB. Analysis of 176 healthy Czech individuals showed presence of only one 5’UTR ANKDR26 variant: c.-140C>G in 21 individuals (11.9%). Image:Summary/Conclusion: We can conclude that most individuals in our cohort (7 out of 9) with the c.-140C>G variant in the 5’UTR of ANKRD26 gene show pathology in platelet aggregation, but only one of them has thrombocytopenia. In addition, three individuals with this gene variant developed malignancy. To answer the above question, whether the ANKRD26 c.-140C>G variant is pathogenic or population polymorphism, functional analysis of this variant must be performed. Our current data show that the ANKRD26 c.-140C>G variant is probably not that pathogenic, as was published.
Assessment of Patient-Reported Outcome Measures for Maternal Postpartum Depression Using the Consensus-Based Standards for the Selection of Health Measurement Instruments Guideline
Authors: Pervez Sultan, Kazuo Ando, Rania Elkhateb, Ronald B. George, Grace Lim, Brendan Carvalho, Ahish Chitneni, Ray Kawai, Tanya Tulipan, Lindsay Blake, Jessica Coker, James O’Carroll
Journal: JAMA Network Open (2022)

Importance Maternal depression is frequently reported in the postpartum period, with an estimated prevalence of approximately 15% during the first postpartum year. Despite the high prevalence of postpartum depression, there is no consensus regarding which patient-reported outcome measure (PROM) should be used to screen for this complex, multidimensional construct. Objective To evaluate psychometric measurement properties of existing PROMs of maternal postpartum depression using the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) guideline and identify the best available patient-reported screening measure. Evidence Review This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. PubMed, CINAHL, Embase, and Web of Science were searched on July 1, 2019, for validated PROMs of postpartum depression, and an additional search including a hand search of references from eligible studies was conducted in June 2021. Included studies evaluated 1 or more psychometric measurement properties of the identified PROMs. A risk-of-bias assessment was performed to evaluate methods of each included study. Psychometric measurement properties of each PROM were rated according to COSMIN criteria. A modified Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the level of evidence supporting each rating, and a recommendation class (A, recommended for use; B, further research required; or C, not recommended) was given based on the overall quality of each included PROM. Findings Among 10 264 postpartum recovery studies, 27 PROMs were identified. Ten PROMs (37.0%) met the inclusion criteria and were used in 43 studies (0.4%) involving 22 095 postpartum women. At least 1 psychometric measurement property was assessed for each of the 10 validated PROMs identified. Content validity was sufficient in all PROMs. The Edinburgh Postnatal Depression Scale (EPDS) demonstrated adequate content validity and a moderate level of evidence for sufficient internal consistency (with sufficient structural validity), resulting in a recommendation of class A. The other 9 PROMs evaluated received a recommendation of class B. Conclusions and Relevance The findings of this systematic review suggest that the EPDS is the best available patient-reported screening measure of maternal postpartum depression. Future studies should focus on evaluating the cross-cultural validity, reliability, and measurement error of the EPDS to improve understanding of its psychometric properties and utility.
P1549: NOVEL SLC4A1 GENE MUTATIONS IN HEREDITARY SPHEROCYTOSIS BAND 3 PROTEIN-DEFICIENT TUNISIAN PATIENTS
Authors: N. TRABELSI, I. Kraiem, S. Menif, S. Abbes
Journal: HemaSphere (2022)

Background: Band 3 is the most abundant transmembrane protein in the erythrocyte, which is encoded by the SLC4A1 gene. Several pathogenic mutations in the SLC4A1 gene, affecting both the cytosolic and the transmembrane domains, are linked to Hereditary Spherocytosis (HS). This inherited disorder causing hemolytic anemia, due to membrane proteins abnormalities. HS is the result of defects that interrupt the vertical interaction including the band 3-ankyrin-spectrin complex. Aims: We aimed to study HS in band 3 protein-deficient patients, identify the causative gene mutations and investigate phenotype-genotype correlations. Methods: Ten HS Tunisian patients were investigated. We assessed red cell fragility parameters and eosine-5-maléimide (EMA), band 3 protein-binding dye, as an indicator of a membrane protein deficiency. We confirmed the EMA flow cytometry analysis by the erythrocyte membrane protein electrophoresis. Finally, we explored SLC4A1 gene mutations through PCR-Sanger sequencing. Different computational methods were used for the interpretation of the novel and known genetic variations effects. Results: We identified eight novel SLC4A1 gene mutations: c.877-1G>A in intron 9, c.1031G>C;p.(Arg344Pro) and c.1034-1036delinsATA;p.(Arg345-Arg346delinsAsnSer) detected in exon 10, c.1192A>T;p.(Thr398Ser) and c.1193C>G;p.(Thr398Arg) in exon 11, c.1364G>A;p.(Gly455Glu) in exon 13, c.2354del;p.(Leu785Argfs*44) in exon 18 and c.2531del;p.(Leu844Argfs*7) in exon 19, as well as twenty-one polymorphisms in HS band 3 protein-deficient patient. The deleterious effect of the new mutations on the protein structure and on splicing process was confirmed using In silico analysis. Summary/Conclusion: Our findings throw light on the molecular basis of HS-band 3 deficient Tunisian patients. The continuous characterization of the molecular defects responsible for membrane protein deficiency improves the diagnosis accuracy and helps to better understand the genetic mechanisms of HS for the early care of each affected individual.
PB1942: HEPATIC MANIFESTATIONS OF CHILDHOOD HEMOPHAGOCYTIC LYMPHOHISTOCYTOSIS
Authors: M. El Sayed, F. Ebeid, S. M. Abd El Kader, F. El-Shorbay, I. Ragab
Journal: HemaSphere (2022)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory disorder caused by benign systemic overgrowth of macrophages in the reticulo-endothelial system leading to cytokine storm. The main features of HLH are; fever, splenomegaly, bi/pancytopenia; hyper-ferritinemia, hyper-triglyceridemia and hypo-fibrinogenemia; which if not diagnosed and early treated progresses to disseminated intravascular coagulation (DIC), multi-organ dysfunction with dismal outcome. Hepatic manifestations are not well recognized primary presentation in pediatric patients with HLH. This presentation mandates high levels of suspicious for early diagnosis. Aims: To study the clinical, laboratory, and pathological hepatic manifestations in patients with HLH at diagnosis and upon reactivation. Methods: A 6 month retrospective cohort study included 35 patients with genetically confirmed HLH divided into familial HLH by its types, X linked lymphoproliferative syndrome and HLH with partial albinism; following at pediatric hematology/oncology clinic, Ain Shams University. In the studied patients, detailed review of patient’s clinical, laboratory data of HLH, hepatic transaminases and synthetic liver functions were done at time of presentation, at week 2, 8 from treatment start and at time of reactivation; Liver biopsy results and genetic analysis were recorded. Biochemical liver involvement was considered when alanine aminotransferase was 3 or more the upper level of normal value at presentation. Overall and reactivation free survival were analyzed according to liver involvement. Results: Thirty five patients with HLH were recruited with age range of 2-108 months at presentation. Twenty patients (62.9%) had genetically confirmed HLH; Twelve (34.3%) of them had MUNC13D mutations, Three (8.6%) had STXBP2 mutation, Five (14.3%) had RAB27A mutation while four (11.4%) had secondary HLH. Overall survival at 12 month was 40% with median event free survival of 3 months.Among studied patients; 29 (82.9%) had hepatomegaly at diagnosis with hepatic reactivation in 51.4%. Eight (22.8%) patients had biochemical liver involvement with transaminase level 6 times above normal at presentation. There was no significant difference in demographic data, clinical presentation, type of mutant gene, and overall or reactivation free survival according to liver involvement. Summary/Conclusion: Variable transaminitis and synthetic liver dysfunction might be the presenting manifestation of HLH and upon reactivation. Significant biochemical liver involvement is an under recognized presentation of HLH. Hepatic involvement did not impact response to treatment and disease outcome.
PB1891: VARIANT PHILADELPHIA CHROMOSOME IN CML
Authors: N. Bouayed Abdelmoula, S. Aloulou, B. Abdelmoula
Journal: HemaSphere (2022)

Background: Chronic myeloid leukemia is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the Philadelphia chromosome and the reciprocal translocation t(9:22)(q34;q11). Almost 5 to 10 percent of chronic myeloid leukemia cases demonstrate variant Philadelphia translocations. Aims: To contribute to the description of patients’ clinical characteristics and prognosis with variant Ph chromosome-positive leukemia, we report a Ph chromosome-positive CML in the chronic phase characterized by an unusual variant Ph chromosome. Methods: An elderly male Libyan patient was suspected to have chronic myeloid leukemia. Cytogenetic and molecular exploration were conducted using bone marrow and blood samples. Cytogenetic analysis was performed on lymphocytes and bone marrow cells after short-term culture (48 hours). The cells were treated with colchicine and hypotonic KCl solution. The pellet was fixed and washed in methanol-acetic acid (3:1). The cells were resuspended in fixative and dropped onto slides. Chromosome-banding analysis was performed using RHG and GTG banding techniques. Three karyotypes and 25 metaphases were analyzed according to the International System for Human Cytogenetic Nomenclature. Multiplex reverse transcription-PCR (RT-PCR) was used to identify the BCR-ABL1 transcript. RT-PCR was performed according to European recommendations, as described previously. Results: Clinical assessment confirmed the first chronic phase of a chronic myeloid leukemia. Chromosomal formula showed an homogeneous structural translocation: t(1;9;12;22)(p35-36;q34;p13;q11) involving four chromosomal regions, 1p35-36, 9q34, 12p13 and 22q11.2. Molecular investigation confirmed the Ph nature of the chromosomal abnormality by showing the BCR-ABL1 transcript. The patient was treated by using Imatinib molecule with a favorable therapeutic response. Summary/Conclusion: A new variant Ph chromosome-positive CML in the chronic phase is reported. It is a four-way Ph translocation t(1;9;12;22)(p35-36;q34;p13;q11) involving four chromosomal regions, 1p35-36, 9q34, 12p13 and 22q11.2. Imatinib, the first-generation TKI treatment was efficient.